During the past 20 years, there has been a dramatic increase in obesity in the United States and these rates remain high. In 2010, no state had a prevalence of obesity less than 20%. Not only does obesity threaten a significant portion of the United States population, but this health crisis is a considerable financial burden as well. There is no shortage of research in the United States in an effort to combat obesity and obesity-related diseases.
Brown adipose tissue (BAT) is a highly metabolic form of fat tissue that natively exists in humans and other mammals. The primary function of BAT is to convert chemical energy to heat through a highly metabolic process of uncoupled respiration (thermogenesis), which is performed by numerous mitochondria containing uncoupled protein 1 (UCP1) in brown adipose cells. Until recently it was thought that adult humans lack functional BAT, however new studies have revealed that some adults have significant amounts of active BAT which may contribute to energy expenditure and maintenance of a lean, non-diabetic phenotype. It was found that adult humans with higher amounts of brown adipose tissue tend not to be overweight or obese, and that BAT levels and activity are negatively correlated with body mass index (BMI) and body fat. Further it has been found in humans that the amount of active BAT decreases with age, providing a potential link between BAT loss and age-related weight gain. The amount of BAT present in humans correlates strongly with lower body fat levels and healthy metabolism.
BAT's mechanism of action is primarily a function of its numerous and large mitochondria, which contain uncoupling protein 1 (UCP-1). Due to the naturally high metabolic rate of BAT (that can account for up to 20% of daily energy expenditure), BAT has great potential as an anti-obesity therapy if the amount and/or activity of BAT can be increased in humans. Adult humans and mice have brown-like or “beige” adipocytes present in white adipose deposits which are normally quiescent, but can become highly thermogenic upon appropriate stimulation. In mice, chronic stimulation through cold exposure or beta-3 adrenergic stimulation increases the extent and activity of BAT-like cells in white fat deposits, a process often called “browning”. Increasing or activating brown or “beige” adipose tissues has been shown to reduce weight and symptoms of diabetes in mouse models (Boström et. al, Nature 481, 463-468, 26 Jan. 2012).
Most current treatments for obesity induce weight loss by reducing caloric intake. However, it has been posed that humans naturally compensate for reduced energy intake by lowering metabolic rate, ultimately limiting the efficacy of such therapies. Other therapies for weight loss and type 2 diabetes (such as bariatric surgery and pharmaceuticals) have had limited success and exhibit numerous side effects and complications. The epidemic of obesity and diabetes, with the additional related complications of heart disease and cancer, present major public health concerns in terms of population health and medical expenses. There is a need for treating and preventing obesity and diabetes symptoms in humans that will potentially have a major impact in reducing the poor health and high costs associated with obesity, diabetes, and associated comorbidities. Harnessing BAT's capacity for increasing energy consumption via thermogenesis provides a therapy that induces weight loss by increasing metabolic rate, rather than limiting absorption of calories and nutrients. Increasing BAT levels in obese patients to similar levels as lean individuals provides the same benefits for reducing body mass and metabolic health in obese individuals, but with enhanced safety and efficacy compared to drugs or bariatric surgery.